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Article

EGFR inhibition enhances the antitumor efficacy of a selective BRAF V600E inhibitor in thyroid cancer cell lines

  • Authors:
    • Yongsheng Jia
    • Cuicui Zhang
    • Chuanxiang Hu
    • Yang Yu
    • Xiangqian Zheng
    • Yigong Li
    • Ming Gao
  • View Affiliations / Copyright

    Affiliations: Thyroid and Neck Department, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin 300060, P.R. China, Department of Thoracic Oncology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin 300060, P.R. China, Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, P.R. China
  • Pages: 6763-6769
    |
    Published online on: February 21, 2018
       https://doi.org/10.3892/ol.2018.8093
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Abstract

BRAF V600E is the most common genetic alteration in thyroid cancer and is indicative of a relatively poor prognosis. A selective inhibitor of BRAF V600E has been proposed as a novel treatment for patients with thyroid cancer exhibiting BRAF V600E mutations. However, this inhibitor has demonstrated a limited therapeutic effect. In the present study, possible adaptive mechanisms of resistance of thyroid cancer cells to the specific BRAF V600E inhibitor, PLX4032, were investigated. MTT assays were performed to determine the anti‑proliferative efficiencies and half maximal inhibitory concentration (IC50) of inhibitory treatments. The level of phosphorylated ERK was used to evaluate the activity of the mitogen assisted protein kinase (MAPK) pathway. Flow cytometry was performed to evaluate the rate of apoptosis. The IC50 measurements of PLX4032 in K1 and BCPAP cells were 0.550 and 1.772 µM, respectively. Co‑treatment with an endothelial growth factor receptor (EGFR) inhibitor decreased the IC50 of PLX4032 to 0.206 µM, and prolonged the inhibitory effect of PLX4032 in K1 cells. In cells treated with PLX4032 alone, the MAPK pathway was reactivated after 24 h. However, the addition of an EGFR inhibitor suppressed this reactivation and increased the rate of apoptosis. In summary, the present study demonstrated that thyroid cancer harboring the BRAF V600E mutation was resistant to a selective BRAF inhibitor due to reactivation of the MAPK pathway. Co‑treatment with an EGFR inhibitor increased antitumor efficacy and suppressed resistance to the BRAF V600E inhibitor.
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Copy and paste a formatted citation
Spandidos Publications style
Jia Y, Zhang C, Hu C, Yu Y, Zheng X, Li Y and Gao M: EGFR inhibition enhances the antitumor efficacy of a selective BRAF V600E inhibitor in thyroid cancer cell lines. Oncol Lett 15: 6763-6769, 2018.
APA
Jia, Y., Zhang, C., Hu, C., Yu, Y., Zheng, X., Li, Y., & Gao, M. (2018). EGFR inhibition enhances the antitumor efficacy of a selective BRAF V600E inhibitor in thyroid cancer cell lines. Oncology Letters, 15, 6763-6769. https://doi.org/10.3892/ol.2018.8093
MLA
Jia, Y., Zhang, C., Hu, C., Yu, Y., Zheng, X., Li, Y., Gao, M."EGFR inhibition enhances the antitumor efficacy of a selective BRAF V600E inhibitor in thyroid cancer cell lines". Oncology Letters 15.5 (2018): 6763-6769.
Chicago
Jia, Y., Zhang, C., Hu, C., Yu, Y., Zheng, X., Li, Y., Gao, M."EGFR inhibition enhances the antitumor efficacy of a selective BRAF V600E inhibitor in thyroid cancer cell lines". Oncology Letters 15, no. 5 (2018): 6763-6769. https://doi.org/10.3892/ol.2018.8093
Copy and paste a formatted citation
x
Spandidos Publications style
Jia Y, Zhang C, Hu C, Yu Y, Zheng X, Li Y and Gao M: EGFR inhibition enhances the antitumor efficacy of a selective BRAF V600E inhibitor in thyroid cancer cell lines. Oncol Lett 15: 6763-6769, 2018.
APA
Jia, Y., Zhang, C., Hu, C., Yu, Y., Zheng, X., Li, Y., & Gao, M. (2018). EGFR inhibition enhances the antitumor efficacy of a selective BRAF V600E inhibitor in thyroid cancer cell lines. Oncology Letters, 15, 6763-6769. https://doi.org/10.3892/ol.2018.8093
MLA
Jia, Y., Zhang, C., Hu, C., Yu, Y., Zheng, X., Li, Y., Gao, M."EGFR inhibition enhances the antitumor efficacy of a selective BRAF V600E inhibitor in thyroid cancer cell lines". Oncology Letters 15.5 (2018): 6763-6769.
Chicago
Jia, Y., Zhang, C., Hu, C., Yu, Y., Zheng, X., Li, Y., Gao, M."EGFR inhibition enhances the antitumor efficacy of a selective BRAF V600E inhibitor in thyroid cancer cell lines". Oncology Letters 15, no. 5 (2018): 6763-6769. https://doi.org/10.3892/ol.2018.8093
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